Dietary Supplements Containing Ephedra Pose Serious Health Risk

November 06, 2000
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A study conducted for the U.S. Food and Drug Administration to assess the safety of popular dietary supplements containing ephedra concludes that these products can pose severe health risks, with sometimes fatal consequences, prompting an urgent need to identify those at greatest risk and establish safe doses. Scientists at UCSF Medical Center who conducted the study also say ephedra-containing products should be more uniformly and explicitly labeled.

The analysis will appear in the Dec. 21 issue of The New England Journal of Medicine. It has been posted early on the journal's web site due to its health implications. The paper draws on a study the UCSF team prepared for the FDA, assessing 140 reports the agency received on adverse effects from supplements containing ephedra. The full report was published in the Federal Register earlier this year.

Of the 140 reports the FDA received, researchers found that just under a third (31 percent), or 43 of the people "definitely" or "probably" suffered an adverse effect from ephedrine in a dietary supplement. Of these 43, three died, seven suffered permanent injury and four more required on-going medical treatment, the report said.

Serious effects included five cardiac arrests - two fatal and three resulting in permanent brain damage and disability; four strokes; and 10 cases of hypertension.

When a second group was included in the analysis - those whose physical symptoms were "possibly" related to ephedrine products - the number of deaths rose to 10 out of 87 people, and permanent disabilities rose to 13 out of the 87.

Ephedrine-containing supplements are used by about 12 million people in the United States, with some 3 billion "servings" sold last year, according to industry statistics. They are stimulants, used for short-term energy boosts to enhance athletic performance and endurance, to help people exercise longer, feel more alert and to dampen appetite. Studies indicate that weight loss with the aid of such products is only temporary. In addition, as people continue to take ephedrine-containing supplements, the body becomes tolerant, and they must take more to get the same effect.

The researchers called for large-scale, controlled studies to quantify the dangers of these products and to identify who is vulnerable to the serious side effects - steps needed to determine a maximum daily safe dose.

The UCSF scientists also urged the FDA to move quickly to impose more uniform, mandatory labeling of contents and quantities. In addition, they said the claimed benefits of these products are questionable and unproven compared with potentially severe risks.

"When I talk to people about taking products containing ephedra to lose a few pounds, I tell them that the products have caused strokes and other severe side effects, and ask them to consider if that is an acceptable risk," said Dr. Christine Haller, lead author of the paper and a post-doctoral researcher in the lab of senior author Dr. Neal Benowitz, a UCSF professor of medicine, psychiatry and biopharmaceutical sciences at the UCSF-affiliated San Francisco General Hospital Medical Center.

"Although 140 serious ill effects may not seem like that many compared to the number of consumers of these products," says Haller, "adverse effects are widely believed to be underreported by 10-fold or more. So, we believe there are many more injuries than are represented by the FDA reports. And with ephedra, the potential risks are not accompanied by any clear benefits."

"We think, that as currently marketed, these supplements are unreasonably hazardous," Benowitz said. "When used as labeled, ephedrine-containing nutritional supplements present a significant and unreasonable risk of injury."

Most of the stimulating supplements are derived from the herbal plant ma huang, and often also contain caffeine derived from guarana.

"Both ephedra and caffeine are stimulant drugs, and when consumed in combination, the stimulation is much more intense," Benowitz said. "When people drink coffee or other caffeine beverages while taking the supplements, the stimulating effect may become even more pronounced."

Dozens of ephedrine-containing products are sold, with a great variability in the accuracy, completeness and adequacy of labels citing ingredients and potential adverse health effects. "There must be more FDA regulatory control," Haller said. "First, uniform product labeling should be enforced, with all ingredients and stimulant quantities specified in a consistent way from product to product." In addition, the FDA must come up with a safe dosing recommendation: a maximum allowable dosage per 24 hours. This may require more research to pinpoint the risk factors, since the researchers suspect but don't know for sure who is at greatest risk, Haller said.

Benowitz said, "Since ephedrine-containing supplements are stimulants, we suspect that the people who should avoid them are those who have kidney disease, those with pre-existing heart disease, high blood pressure, over-active thyroid, or psychiatric disorders, and those with autonomic insufficiency -- abnormalities in the nerves controlling their cardiovascular system - and those with histories of seizures and diabetes."

The full report Haller and Benowitz prepared for the FDA is found in the Federal Register, Vol. 65, issue 64, April 3, 2000. It is Federal docket #00N-1200. The FDA report was titled "Review of Adverse Reaction Reports Involving Ephedrine-containing Herbal Products." More information on the FDA report can be found at: www.accessdata.fda.gov/scripts/oc/ohrms/index.cfm.

The research was supported by funds from the Food and Drug Administration, the National Institute on Drug Abuse, National Institutes of Health.